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Biomedical subjects

R A Ward

Publications and source records attributed to R A Ward.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effects of hemodialysis on platelet-derived thrombospondin.

The effects on platelet-derived thrombospondin (TSP) of hemodialysis with a cellulose membrane were studied in patients during routine hemodialysis and in normal subjects using an ex vivo model. Plasma and platelet-bound TSP were determined pre- and post-dialysis, in blood entering and leaving the dialyzer after 1, 3, 5, 15, and 30 minutes of dialysis, and in blood leaving the ex vivo module after 5, 10, 15, 20, and 25 minutes of perfusion. Plasma concentrations of beta-thromboglobulin (beta TG) and thromboxane B2 (TxB2), and platelet membrane expression of the alpha-granule protein GMP-140, were also measured. Significant increases in plasma concentrations of TSP and beta TG occurred between the inlet and outlet of the dialyzer after 5, 15, and 30 minutes of dialysis, accompanied by a slow, but significant, increase in their arterial plasma concentrations. In contrast, initiation of dialysis was associated with an immediate increase in plasma TxB2 concentration between the inlet and outlet of the dialyzer and an abrupt increase in arterial plasma TxB2 concentration which plateaued at 250% of the pre-dialysis value after five minutes. Transit of platelets through the dialyzer had no effect on platelet-membrane-associated TSP or GMP-140. Plasma TSP and beta TG concentrations at the outlet of the ex vivo module also increased significantly during perfusion, but plasma TSP concentrations were twofold greater than those during hemodialysis. In vitro stimulation of platelets with thrombin and immunoblotting studies of platelet release proteins showed reduced TSP release by platelets of hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of extracorporeal membrane oxygenation on leukocyte function in neonates.

The impact of extracorporeal membrane oxygenation (ECMO) on neonatal leukocyte content and function was examined in six patients. Patients were treated with ECMO for a mean of 134 h (range 44-246 h). Absolute neutrophil counts decreased from 14679 +/- 2291/mm3 to 7791 +/- 1672/mm3 after 2 h of ECMO. However, neutrophil phagocytosis and oxidative burst remained unchanged during the first 48 h of bypass. Monocyte counts also decreased during bypass, and at times were undetectable in 50% of patients. Monocyte HLA-DR content was decreased compared to normal cord blood prior to initiation of ECMO, and remained low throughout ECMO. However, the content increased significantly after termination of bypass. Plasma C3a levels increased transiently, paralleled by an increase in neutrophil CR3 expression. While moribund infants had some impairment of host defenses prior to ECMO, there was no further impact of ECMO per se on the parameters measured, other than transient complement activation and decreased monocyte counts.

Complement Activation↗
PubMed1991

Understanding the regulatory requirements for dialysate.

It is important for providers to remember that dialysate is considered by federal regulatory agencies to be a medical device, but that most of the regulations are aimed at the manufacturers. The manufacturers are subject to FDA inspection and they must comply with Good Manufacturing Practices. Once the product reaches the provider's door, the manufacturer's responsibility ends, as does most close regulation. The best way for facilities to protect themselves is to develop a good quality assurance program that establishes and maintains policies and procedures which will ensure safe and effective use of dialysate.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1990

Quantitative analysis of gamma-aminobutyric acid (GABA) receptors of Purkinje cell layer from rat cerebellar slices.

1. Extracellular recordings were made from Purkinje cell layer of rat cerebellar slices. Cell activity was sensitive to both magnesium and manganese ions. 2. Glutamic and aspartic acids both excited cell activity while gamma-aminobutyric acid (GABA), muscimol, taurine, beta-alanine and delta-aminolaevulinic acid all inhibited activity. 3. The sensitivity to GABA varied with depth while no such effect was observed with muscimol. 4. Bicuculline methiodide, picrotoxin and pitrazepin blocked the action of muscimol with pA2 values of 5.92, 5.97 and 5.71 respectively. 5. The benzodiazepines flurazepam and RU 32007 both potentiated the GABA inhibition and this potentiation was blocked by Ro 15-1788, a benzodiazepine antagonist.

Animals↗
PubMed1990

Evaluation of phagocytic cell function in an ex vivo model of hemodialysis.

An ex vivo model of hemodialysis was used to evaluate the effect of dialysis membranes on phagocytic cell function. Blood was withdrawn continuously from healthy, non-uremic donors, heparinized, and pumped, single pass, through membrane modules under conditions which simulated normal dialysis conditions. The membrane modules contained membranes of cellulose, DEAE-substituted cellulose, or polysulfone. Blood was obtained from the module outlets for determination of complement activation, phagocyte elastase release, zymosan-induced phagocyte chemiluminescence, and monocyte interleukin-1 production. Significantly less complement activation occurred with the polysulfone and DEAE-substituted cellulose membranes than with cellulose membranes. Normal monocyte interleukin-1 production was not stimulated by any of the membranes used. In contrast, the cellulosic, but not the polysulfone, membranes primed the oxidative burst of the phagocytes and caused them to release elastase. DEAE-substituted cellulose had a lesser effect on elastase release than did cellulose and elastase release correlated significantly with the degree of complement activation. However, the correlation between complement activation and priming of phagocyte oxidative burst was weak, suggesting that membranes affect phagocyte oxidative metabolism through more than one mechanism. We conclude that some dialysis membranes stimulate the bacteriacidal functions of normal phagocytic cells, in part through complement-dependent mechanisms.

Humans↗
PubMed1990

Differential activation of monocytes in haemodialysis patients exposed to different types of membranes.

Peripheral blood mononuclear cells (PBMC) from haemodialysis patients treated with different types of membranes were isolated, incubated in vitro, and extracellular and cell-associated interleukin I (IL-1) assayed by radioimmunological methods. Extracellular IL-1 was low and not different from controls, regardless of the dialyser used. In contrast, cell-associated IL-1 was increased in patients treated with dialysers containing low-flux Cuprophan (CU, n = 5) and polyacrylonitrile sheet membrane (AN69, n = 5). Patients treated with dialysers containing high-flux polysulphone (PS, n = 7), and polymethylmethacrylate (PMMA, n = 8), exhibited no increase in cell-associated IL-1 under these conditions. To elucidate the mechanism of the activation, aqueous extracts of dialysers containing CU, PS, and AN69 were tested for their ability to induce IL-1 generation in PBMC from healthy donors. Extracts from unrinsed CU-containing dialysers caused significant IL-1 synthesis and release, whereas incubation with extracts from dialysers containing PS and AN69 sheet membranes did not. Hence, although both CU and AN69 sheet-type dialysers result in activation of blood monocytes the mechanism of action appears to be different. We speculate that functional signs of PBMC activation as evidenced by increased spontaneous IL-1 production observed in some patients on long-term haemodialysis may result from extractable dialyser membrane material while in other instances direct cell membrane interactions or endotoxin transfer from the dialysate may be relevant.

Adult↗
PubMed1990

Age and patterns of HMO satisfaction.

Consumerism and increasing complexity in health care options highlight the importance of health care satisfaction. Patterns and sources of satisfaction are assessed for health maintenance organizations (HMOs), a relatively novel option, using national survey data. Particular attention is paid to age differences, because HMO Medicare coverage is a recent development and older people generally express little HMO familiarity or receptivity. Higher satisfaction is expressed by HMO members than by nonmembers for both younger and older persons. HMO satisfaction is higher for older than for younger members, a pattern at odds with nonmember attitudes about HMOs. Member satisfaction is a function of the nature of patient/provider ties and related attitudes, as it is among nonmembers. Importance of a "regular" provider is particularly evident among older HMO members. Patterns of HMO satisfaction among older members likely reflects both cohort differences and age-associated patterns of health and related attitudes.

Adult↗
PubMed1989

The impact of erythropoietin on hemodialyzer design and performance.

The present study investigated theoretically and experimentally the effects of increases in hematocrit on the clearance of urea by the Baxter ST15 hollow fiber dialyzer. In a theoretical model that incorporates the three component resistances for the overall mass transfer rate, namely, the resistance of the blood (Rb)-, membrane (Rm)-, and dialysate side (Rd), it was predicted that a change in hematocrit would alter only the blood side resistance. The overall impact of this alteration is expected to be determined by the relative contribution of Rb to the overall resistance (RO). The modest contribution of Rb to RO implies that a major change in Rb (50%) would have only a minor effect on RO (11%) and consequently on urea clearance (5%). These theoretical conclusions were tested experimentally and the results confirmed the theoretical predictions. Indeed, there was little change in urea clearance in the clinically relevant range of variations in hematocrit (19-39%). Possible ways of compensation by minor changes in the hollow fiber geometry are discussed as well as the more complex relationships with larger solutes (creatinine) or unequally distributed solutes (potassium, phosphate).

Equipment Design↗
PubMed1989

Polymorphonuclear leukocyte function during hemodialysis: relationship to complement activation.

Phagocytosis, H2O2 production, and C3bi receptor (CR3) expression by polymorphonuclear leukocytes (PMN) obtained from patients before, during, and after a hemodialysis treatment were evaluated by flow microfluorometry. The results were compared to changes in plasma levels of C3ades Arg and C5ades Arg. Prior to hemodialysis C3ades Arg and C5ades Arg levels, CR3 expression and phagocytosis were not different from normal controls. However, both basal and phagocytosis-induced H2O2 production were increased. C3ades Arg and C5ades Arg were increased after 15 min of dialysis; this was accompanied by transient but significant reductions in PMN count and phagocytosis and increased CR3 expression. No changes in basal or stimulated H2O2 production were observed. We conclude that PMN of hemodialysis patients are primed for an enhanced respiratory burst before dialysis is initiated. Dialysis-induced complement activation after the initiation of dialysis does not further stimulate H2O2 production or enhance the response to phagocytosis. However, complement activation may cause leukopenia and CR3 expression.

Complement Activation↗
PubMed1989

Age differences in HMO receptivity.

The changing health care market has highlighted the role of the individual in choosing health care providers. HMOs are a relatively novel option, particularly for Medicare beneficiaries. National survey data are used to assess patterns of HMO receptivity. Older persons are less familiar with the HMO model. They also express less favorable attitudes toward HMOs and less enrollment interest. HMO receptivity is a function of health care attitudes and experiences and the nature of available information about HMOs. Age differences in HMO receptivity reflect the effects of cohort membership and aging on these factors.

Adult↗
PubMed1989

Activation of mononuclear cells by aqueous extracts from hollow-fibre haemodialysers.

Monocytes from patients treated by long-term haemodialysis with cellulosic membranes can show functional signs of activation depending on the dialyser module. To elucidate the mechanism of this phenomenon, aqueous extracts of various hollow-fibre dialysers were tested for their ability to induce in-vitro interleukin-1 generation in peripheral blood mononuclear cells from healthy donors. Extracts were prepared by passing 0.5 litres of sterile endotoxin-free water from the dialysate to the blood compartment of the dialyser. Different dialysers containing cellulosic membranes, i.e. cuprophan, and hemophan, were studied. Extracts were dried by lyophilisation and resuspended in cell culture medium before incubation with peripheral blood mononuclear cells for 18 hours at 37 degrees C in a 5% CO2 atmosphere. Interleukin-1 was assayed by biological or radioimmunological methods. Extracts from steam-autoclaved, dry-stored, or gamma-sterilised, wet-stored cuprophan and hemophan modules resulted in interleukin-1 activity that did not differ from negative controls. By contrast, extracts from cuprophan caused significant interleukin-1 production when prepared from ethylene oxide-sterilised, dry-stored dialysers. This monokine-inducing activity could not be neutralised by the addition of polymyxin B and was heat unstable, indicating that the cell-activating stimulus was not endotoxin. Extensive rinsing of the module with water before extract preparation totally mitigated the in-vitro production of interleukin-1. Our results suggest that the extract-induced activation of peripheral blood mononuclear cells found with some dialysers containing membranes of cellulosic origin cannot be exclusively related to the membrane polymer, but depends on a number of other parameters such as sterilisation and storage mode of a given membrane.

Adjuvants, Immunologic↗
PubMed1989

Review of new Nearctic mosquito distributional records north of Mexico, with notes on additions and taxonomic changes of the fauna, 1982-89.

During the past 7 years, 24 species of Nearctic mosquitoes have had extensions to their known distribution in the form of 32 new state and province records in the United States and Canada. They are included in this report along with relevant references. Additionally, 3 new United States country records have been established, 3 species have had name changes, a new species of Anopheles and sibling species of another anopheline have been described. Details of these occurrences are covered.

Animals↗
PubMed1988

Immunologic complications of long-term implantation of a total artificial heart.

Bacterial infections are a significant complication of long-term total artificial heart implantation. We evaluated the functional capabilities of host defense mechanisms in two patients sustained long-term by a total artificial heart. Although serum complement and polymorphonuclear leukocyte function remained intact, both patients became B and T lymphopenic and there was an initial decrease in the ratio of helper/inducer to suppressor/cytotoxic cells. Histologic examination of their lymphoidal tissue at autopsy further revealed reduced numbers of germinal centers and atrophy of the T lymphocyte-dependent areas. In addition, the reticuloendothelial system was engorged with degenerate erythrocytes. We hypothesize that blockade of the reticuloendothelial system was induced by multiple blood transfusions necessitated by device-associated hemolysis and coagulopathy. This blockade may have led to a progressive loss of content of the antigen-specific lymphoidal elements and, perhaps, to a reduced ability to ingest microbe-antibody complexes.

Bacterial Infections↗
PubMed1988

Rapid measurement of dialyzer clearance as a function of molecular weight.

The relationship between solute clearance and molecular weight (MW) is an important performance characteristic of hemodialyzers. Traditionally, this relationship has been determined using a range of solutes of diverse properties that require a variety of analytical procedures. We describe a simple method for obtaining clearance as a function of MW using a homologous series of glucose oligomers, continuous from the monomer to the octamer. Using HPLC, single analyses of the inflow and outflow streams of the dialyzer allow the determination of clearances over a MW range of up to 1314 daltons.

Calibration↗
PubMed1988

Altered interleukin-1 production in patients undergoing hemodialysis.

The capacity of peripheral blood mononuclear cells (PBMC) to undergo spontaneous and induced interleukin-1 (IL-1) production was examined in 10 healthy controls and in 10 patients undergoing intermittent hemodialysis (HD) using cuprophane membranes. Extracellular and cytoplasmic IL-1 activity was assayed by biologic and radioimmunologic methods. Spontaneous extracellular IL-1 activity was low in the patient and the control groups. However, spontaneous cytoplasmic IL-1 activity was greatly increased in the patients. Both assays gave comparable results. In contrast, the IL-1 response to lipopolysaccharide was significantly decreased in PBMC from the patients compared to controls. From these results we conclude that PBMC from HD patients show functional signs of activation, but an impaired response to exogenous stimuli, such as endotoxin.

Adult↗
PubMed1987

Hemodialysate composition and intradialytic metabolic, acid-base and potassium changes.

We compared the effects of dialysate composition on changes in intermediary metabolites, acid-base balance, and potassium removal during hemodialysis. Patients were dialyzed against dialysates containing acetate or bicarbonate, each with or without glucose, in a four-way cross-over study. Dialysates containing acetate were associated with significant perturbations in intermediary metabolism, including increases in blood citrate, acetoacetate and beta-hydroxybutyrate and a decrease in pyruvate. In contrast, bicarbonate-containing dialysates caused minimal perturbations in intermediary metabolism. Addition of glucose to the dialysate decreased the changes in intermediary metabolites; however, the magnitude of this effect was less than that observed for the change from acetate to bicarbonate. Use of acetate also resulted in lower post-dialysis blood-concentrations of base equivalents than obtained with bicarbonate; this difference was unaffected by the presence or absence of glucose. Although pre- and post-dialysis potassium concentrations were unaffected by the dialysate formulation, total potassium removal was significantly greater when glucose was omitted from the dialysate. Our results suggest that both bicarbonate and glucose should be included in the dialysate, particularly for those patients whose capacity for metabolism may be limited because of highly efficient dialysis, intercurrent illness, or starvation. However, addition of glucose to the dialysate may require a reduction in dialysate potassium to maintain proper potassium homeostasis.

Acetates↗